Rapidly disintegrating methylcellulose tablets

ABSTRACT

The present invention relates to a novel pharmaceutical composition and process for preparing swallowable methylcellulose tablets that disintegrate rapidly and meet USP standards in 0.1N hydrochloric acid as well as water.

This application is a 371 of PCT/US98/17405 filed Aug. 21, 1998 whichclaims benefit of 60/056,899 filed Aug. 22, 1997 and 60/087,662 filedJun. 02, 1998.

FIELD OF THE INVENTION

The present invention relates to an improved process for preparingcompressed methylcellulose containing tablets which meet USPdisintegration standards.

BACKGROUND OF THE INVENTION

The history of cellulose ethers, such as methylcellulose andcarboxymethylcellulose suggests that these agents are effective as bulklaxatives. Their mechanism of action involves increasing both the watercontent of, and the bulk content of the stool, as well as lubricatingthe stool; thereby relieving constipation.

Cellulose ethers have been administered as bulk laxatives in dosageforms comprising of tablets, suspensions, and bulk powders; the latteras sugar-free or in compositions containing high amounts of sugar.

Cellulose ethers administered as suspensions in water may contain highconcentrations of sucrose or other sugars and flavors. In suchformulations, the sugar competes with the cellulose ether for availablewater, thereby preventing the cellulose ether from hydratingsufficiently to form a gel. The advantages of using a suspensionformulation is that the cellulose ether is dispersed sufficiently toavoid any significant lumping in the digestive tract. However, thesesuspensions are viscous, semi-gelatinous, and visually unappealing tothe consumer. Another disadvantage is the unpalatability of thesuspensions due to the slimy mouth feel and extreme sweetness of suchsuspensions. Hence, these dosage forms have not gained significantconsumer acceptance.

Bulk powders of cellulose ethers often exhibit lumping of individualparticles and gelation and thus, remain undissolved as they pass throughthe digestive tract. Additionally, administration of bulk powders hascaused cramping, nausea, and vomiting in some patients. Therefore, bulkpowders are not the preferred dosage form for cellulose ethers.

Palatable and visually appealing bulk powders have, however, beenaccomplished by addition of water or another aqueous liquid to a drypowder mix of a water-soluble cellulose ether and a dispersingagent/sweetening component, typically sugar. This technology isdisclosed in South African patent No. 84,1044, published Sep. 26, 1984.The pitfall with these compositions is that they contain about 400calories of nutritive value per dose, primarily due to the high sugarcontent. This high caloric value is not acceptable to the averageconsumers or to users suffering from blood sugar disorders, includingdiabetics. Elderly people are normally, the common strata of thepopulation that suffers from constipation and the more frequent users oflaxatives, and are also commonly suffering with blood sugar disorders.The consumption of large quantities of sugar could aggravate blood sugardisorders.

Sugar encrusted cellulose ethers have been proposed as alternatives tothe bulk powders containing high amounts of sugar. Such formulationshave 1) less sugar such as natural sugar or combination of sugars suchas sucrose, glucose, fructose or corn syrup solids; 2) lower caloricvalue; and 3) are readily dispersed in cold aqueous liquids.

Citrucel® Orange Flavor, a bulk forming laxative containingmethylcellulose as its active ingredient, was first introduced into themarket in 1986. This product contains 15 g of sucrose in a 19 g adultdose, which corresponds to a 2 g dose of methylcellulose. To decreasethe sugar content of this product, a natural flavored formula lower incaloric value, and containing only 1 g sucrose, was developed andintroduced in 1988. Additional patent protection for this product hasfocused on producing a sugar-free and virtually calorie-free powder. Theproduct has a sugar-free sweetener, a dispersing agent, otherexcipients, and flavoring and was marketed in 1991 as Sugar FreeCitrucel® Orange Flavor.

There still remains a need in the art to develop a rapidlydisintegrating solid dosage form of a bulk agent, preferablymethylcellulose, which is convenient to take and transport, sugar free,and easily administered to the consumer having blood sugar disorders ordiabetics, for instance.

SUMMARY OF THE INVENTION

The present invention relates to an improved process for preparingmethylcellulose tablets which are readily dispersible and meet UnitedStates Pharmacopoeia standards for disintegration. The methylcelluloseis compressed into tablets which contain an edible calcium salt, inpreferred w/w ratios. Preferably the tablets rapidly disintegrate,in-vitro in 0.1 N hydrochloric acid and water at 37 ^(±)0.5° C.

DETAILED DESCRIPTION OF THE INVENTION

There is a common belief that tabletted cellulose ethers do not readilydissolve in the digestive tract because these cellulose ethers arehighly hygroscopic. The outer portion of the tablet is said to form agel-like hydrate that prevents the tablet from breaking up and greatlyretards the hydration of the inner portion of the tablet. The presentinvention overcomes this art recognized problem and involves preparationof a novel composition, and process of making, by which a rapidlydisintegrating tablet of methylcellulose is prepared.

The tablets are prepared by a novel process involving a high-shear wetgranulation method, followed by fluidized bed drying, milling, mixingwith the other ingredients, and compression.

The present invention is to a methylcellulose tablet which comprisesmethylcellulose having a viscosity of >1000 centipoise, and at least oneexcipient selected from an edible calcium salt. It is recognized thatthe formulation will also include diluents and fillers well known to theskilled artisan.

The tablet formulations of the present invention are advantageous overother dosage forms of methylcellulose because of their convenience ofadministration and rapid disintegration. This is in contrast to tabletsof methylcellulose, formulated as 100% w/w methylcellulose in a 0.5 gmcaplet which have been found not to disintegrate in 0.1N HCl solution,using a conventional dissolution apparatus even after two hours. Thepresent tablets should disintegrate in 0.1N HCl from about 20 to about30 minutes, preferably from about 10 to about 19 minutes, and morepreferably less than 10 minutes; and in water, the tablets shoulddisintegrate from about 25 to about 30 minutes, preferably from about 15to about 24 minutes, and more preferably less than 15 minutes.

It has been found that low molecular weight (mw) methylcellulose is lesseffective for use as a laxative, and therefore is less desirable for usein a rapidly disintegrating tablet formulation Higher molecular weightmethylcellulose is therefore both desirable and necessary in the presentinvention. The fibers must have a sufficient viscosity to gel and retainwater in the gut to provide the stool bulking and softening for laxationuse.

By using the testing methods for methylcellulose under standardconditions, such as those found in the USP XXII, p. 894, ApparentViscosity method for Methylcellulose, or as discussed in Handbook ofPharmaceutical Excipients, APhA, a preferred methylcellulose for useherein should have a viscosity of >1000 centipoises (cps),preferably >2000 centipoises, more preferably >3000 centipoises, andmost preferably >4000 centipoise. Higher molecular weightmethylcellulose than those described is also desirable, however, thecommercially availability of this grade of methylcellulose being thelimiting feature. At present the upper limit commercially available isabout 6000 cps, which is encompassed within the scope of this invention.One presently available methylcellulose product for use herein isMethocel A4M, made by Dow Chemical Company, Midland Michigan as DowMethocel A4M, having a viscosity of about 3000 to about 5,600 cps, whichis within 75 to 140% of the desired target viscosity herein.

Some of the additional diluents or fillers for use in this formulationare preferably swellable agents, and may include, but are not limitedto, various grades of microcrystalline cellulose, such as Avicel PH 101,Avicel PH 102, & Avicel PH 200; Corn starch; or Starch 1500.

The edible calcium salts suitable for use herein include but are notlimited to, dibasic calcium phosphate dihydrate, calcium phosphateanhydrous, and tribasic calcium phosphate; or mixtures thereof. Apreferred edible calcium salt is the dibasic calcium phosphate dihydratesalt, which salt also provides good compressibility.

If microcrystalline cellulose is added, it is preferably from about 50to 180 microns in size, more preferably about 50. Avicel PH 101 has amean particle size of about 50; Avicel PH 102 has a mean particle sizeof about 100; and Avicel PH 200 has a mean particle size of about 190microns. Preferably the preferred microcrystalline cellulose is AvicelPH 101.

It is noted that the ratio of methylcellulose to edible calcium salt,and additional diluents will depend upon the diluent chosen, and iswithin the skill of the art to determine with preciseness the necessaryratios.

Suitable ratios for particular diluents however, are described below:

For Methylcellulose:Dibasic calcium phosphate, dihydrate, from about 2to about 4:1, preferably from about 2.6-3.1:1;

For Methylcellulose:Calcium phosphate, anhydrous from about 2 to about4:1, preferably from about 3.1:1

Methylcellulose:Tribasic calcium phosphate, WG® from about 2 to about4:1, preferably from about 3.1:1

For Methylcellulose: microcrystalline cellulose, from about 2:1 to about14:1. Preferably for Avicel PH 101 from about 2.2-13.5:1; for Avicel PH102 from about 2.4-8.3:1; and for Avicel PH 200 from about 2.4-4:1.

For Methylcellulose:Corn starch from about 7.5 to about 15, preferablyfrom about 13.5:1;

For Methylcellulose:Starch 1500, from about 2.0 to about 5.0:1,preferably from about 2.4: 1;

For Methylcellulose:Explotab, from about 5 to about 25:1, preferablyfrom about 8.1 to about 21.3:1.

It is recognized that with the edible calcium salt, the formulation mustalso have an ingredient which keeps the granules together, i.e. abinding agent. A preferred binding agent is PVP, or the alternativeagents noted below.

In addition to the above noted edible calcium salt(s), optional diluentsor fillers, and binding agent(s), the formulation may also includeadditional components such as, but are not limited to, a wetting agent,(super)disintegrant(s), a second binding agent(s), dye(s) or colouringagents, and lubricants, which are preferably used to prepare a tabletthat is wetted readily, and is rapidly disintegrated in 0.1Nhydrochloric acid and water, the USP test standard test formethylcellulose.

A preferred wetting agent is sodium lauryl sulfate.

A preferred lubricant is magnesium stearate.

A preferred binding agent is polyvinylpyrrolidone, or PVP, such asPovidone 29K/32. Preferably, the PVP is present in an amount of about 4to about 6.5% w/w.

A preferred disintegrating agent is sodium starch glycolate, such asExplotab®. Preferably, the sodium starch glycolate is present in anamount of about 3 to about 8% w/w.

As various excipents and diluents will be formulated together, and usedin combination herein, suggested % w/w ratios for various formulationsare presented below. While not all of these ratios include the ediblecalcium salts, these are merely illustrative of the invention and theskilled artisan will readily recognize how to formulate the product ofthis invention with the addition of the edible calcium salts.

Sodium lauryl sulfate:Explotab: Dibasic calcium phosphate,dihydrate:Povidone 29K/32: Magnesium stearate include:0.38-0.40:3.5-7.9:20.6-24.8:4.0-6.5:0.5-1.0

Sodium lauryl sulfate:Explotab:Tribasic calcium phosphate WG®: Povidone29K/32: Magnesium stearate include: 0.40:3.5:21.6:6.4:1.0

Sodium lauryl sulfate: Explotab: Calcium phosphate, anhydrous: Povidone29K/32: Magnesium stearate include: 0.40:3.5:21.6:6.4:1.0

Methylcellulose:sodium lauryl sulfate (SLS), from about 60 to about170:1, preferably from about 155:1-170:1;

Methylcellulose:Povidone, preferably PVP 29K/32, from about 8 to about22:1, preferably from about 10.4:1-16.7:1;

Methylcellulose:Magnesium stearate from about 50 to about 150;1,preferably from about 58-132:1;

Sodium lauryl sulfate:Explotab:Avicel PH 101®: Povidone 29K/32:Magnesium stearate include:0.35-0.46:3.05-6.17:4.38-27.13:4.38-6.66:0.76-1.14

Sodium lauryl sulfate:Explotab:Avicel PH 102®: Povidone 29K/32:Magnesium stearate include:0.35-0.46:4.9-6.17:9.21-25.53:4.38-6.66:0.76-1.14

Sodium lauryl sulfate:Avicel PH 200®: Povidone 29K/32: Magnesiumstearate include: 0.38-0.42:19.27-25.53:5.99-6.66:0.94-1.04

Sodium lauryl sulfate:Explotab:Corn starch: Povidone 29K/32: Magnesiumstearate include: 0.36-0.38:3.66-7.07:4.35-4.68:4.35-4.68:0.88-0.95

Sodium lauryl sulfate:Explotab:Starch 1500®: Povidone 29K/32: Magnesiumstearate include: 0.36-0.38:3.66-7.07:24.05-25.89:4.35-4.68:0.88-0.95

Not wishing to be limited to the explicit excipients noted above, thefollowing alternative agents may also be used herein.

Alternatives lubricants to magnesium stearate include, but are notlimited to, calcium stearate, sodium stearate, Cab-O-Sil, Syloid,stearic acid and talc.

Alternatives binding agents to PVP include but are not limited to,hydroxypropylcellulose, hydroxypropyl methylcellulose, acacia, gelatin,tragacanth, pregelatinized starch and starch.

Alternatives disintegrants to Explotab® include but are not limited to,sodium carboxymethylcellulose, Ac-di-sol®, carboxymethylcellulose,veegum, alginates, agar, guar, tragacanth, locust bean, karaya, pectin,and crospovidone.

Alternative wetting agents to sodium lauryl sulfate, include but are notlimited to, magnesium lauryl sulfate.

All of these formulations can be prepared with and without sugar. Asugar-free formulation has the advantage that it can be administeredeasily to consumers with blood sugar disorders or to diabetics in needof such preparations.

Another advantageous property of the present invention is that theformulations contain calcium, such as dibasic calcium phosphatedihydrate. These formulations, for instance, will contain approximatelyan 80 mg/dose, anticipating formulating a 0.5 gm/tablet X 2 tablets/doseof methylcellulose. If desired the amount of calcium can be increased inthese tablets to provide increased therapeutic value to the consumer.

The amount of methylcellulose present in each dose, as well as thenumber of doses of laxative taken per day, will depend somewhat on theage, sex, size of the patient, severity of the patient's particularproblem, the advice of the treating physician, if any, and theparticular taste and habits of the patient. Accordingly, the tablets ofthis invention are advantageously administered in a single dose whichmay contain as much as 500 to 1000 mg of methyl cellulose tablet, or ina plurality of smaller doses containing as little as 250 mg per tablet.Most preferably, for laxative effect, each tablet will contain about 500mg methylcellulose and the patient may take 1 to 2 tablets per dose.This dosage, of 1000 mg should adequately provide optimal laxativeefficacy. Therefore, a preferred range of methylcellulose per tablet isoptimally from about 450 to 550 mg, preferably about 500 mg; oralternatively from about 200 to about 300 mg for a smaller tablet,preferably about 250 mg; or even in increments of about 125 mg tablet,i.e. 75 to 175 mg per tablet.

While preferably the compressed tablets are uncoated, they may, ifdesired, be coated with any suitable coating agent well known in theart. Suitably the coating agents are those used for immediate releasepurposes and will dissolve in the gastric juices. Such coating agentsare well known to those skilled in the art and include, but are notlimited to hydroxypropyl methylcellulose, or methyl cellulose, or 20%w/w Opadry II, orange in water.

As will readily be seen by the working examples, there are variouscombinations of intra and extragranular mixing which are possible usingthe ingredients herein. All are encompassed within the scope of thisinvention. Generally, the high viscosity methylcellulose, such asMethocel A4M, will first be granulated with a binder, such as povidone,a wetting agent, such as sodium lauryl sulfate, and a suitable colouringagent to form the intragranular mixture which is then granulated. Thesegranular components are then admixed with additional wetting agents, anddisintegrating agents and finally blended with lubricant. This finalgranular mixture is then blended and compressed into the tablets of thepresent invention.

Therefore, an aspect of the present invention is a process for preparinga tablet formulation which comprises

a) blending together to form an intragranular mixture high viscositymethylcellulose of >3000 cps, a wetting agent, povidone or sodium starchglycolate, and an edible calcium salt; and

b) adding to the mixture of step (a) a PVP aqueous solution, oralternatively spraying the mixture of step (a) with a PVP aqueoussolution; and preparing granulates; and

c) blending together an extragranular mixture of an edible calcium salt,a wetting agent; a lubricating agent; povidone or sodium starchglycolate or a mixture thereof; and

d) compacting the granulates of step (b) with the extragranular mixtureof step (c).

Another aspect of the present invention is a process for the manufactureof a pharmaceutical tablet, which process comprises mixing

a) granulates comprising high viscosity methylcellulose of >3000 cps, awetting agent, povidone or sodium starch glycolate, an edible calciumsalt; and

b) blending together an extragranular mixture of an edible calcium salt,a wetting agent; a lubricating agent; povidone or sodium starchglycolate or a mixture thereof; and

c) compacting the granulates of step (b) with the granular mixture ofstep (a); and

d) compressing into a tablet.

Another aspect of the present invention is the method of relievingconstipation by increasing the water content of the stool, or byproviding a lubricating effect on the stool in a mammal in need thereof,which method comprises administering to said mammal, an effective amountof a high viscosity methylcellulose compressed into a tablet with asuitable diluent.

METHODS OF PREPARATION

The following examples illustrates the invention but is not intended tolimit the scope thereof. All parts and percentages are by weight unlessotherwise indicated. The disintegration time of the formulationsdescribed in the Tables below were obtained by using a conventionaldisintegration apparatus.

EXAMPLE 1

TABLE I Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 67.27 Dibasic Calcium phosphate,dihydrate 0.0370 4.98 Sodium lauryl sulfate 0.0015 0.20 Dye/Colouringagent 0.0010 0.13 Povidone 29K/32 0.0480 6.46 DI water q.s. q.s. Phase BPhase A 0.5875 79.04 Sodium lauryl sulfate 0.0015 0.20 Sodium starchglycolate 0.0260 3.50 Dibasic Calcium phosphate, dihydrate 0.1245 16.75Magnesium stearate 0.0038 0.51 TOTAL 0.7433 100.00

The process of preparing the rapidly disintegrating tablet ofmethylcellulose is carried out using specified quantities ofingredients, such as those mentioned in TABLE I above, using thefollowing steps:

1. Preparation of Povidone K29/32 (PVP) Solution

The specified amount of PVP was weighed and added to the weighedquantity of water and stirred till all the PVP was dissolved completely.

2. Preparation of Phase A

Accurately weighed amounts of Methocel A4M, calcium phosphate, dibasicdihydrate, sodium lauryl sulfate, and colouring agent, such as anysuitable FD&C Aluminium lake, were transferred to a Key Hi-sheargranulator and mixed for about 10 minutes with impellor speed at 135 rpmand chopper speed at 10%. The PVP solution was sprayed onto the mixturein the granulator at a rate of approx. >200 mL/min. Once addition of PVPsolution was complete, the chopper was stopped. The mixing was continuedin the granulator till resistance reads about 130-135 watts and the timenoted to reach that wattage. A sample was withdrawn from the wetgranulation to record loss on drying (% LOD). The moist granules weredried in the Aeromatic Fluid bed dryer in portions till the % LODreading approximated 1.0-3.0%. The temperature of the air in the fluidbed dryer was maintained at approx. 90-95° C. and the sample was foundto be dry at an outlet air temperature of approx. 32-52° C. The driedgranules were milled through a 12# screen in the Fitz Mill at a highspeed. The granules were weighed and percent yield calculated. Themoisture content was measured for the dry granules. A sample from thegranules was withdrawn and analyzed for particle size distribution, bulkand tap density, flow index, and moisture studies. The granules wereweighed and ingredients of Phase B were calculated based on the weightof remaining granules.

3. Preparation of the Final Blend

To the weighed milled granules produced in Phase A above, specifiedamounts of sodium lauryl sulfate, sodium starch glycolate (Explotab®),and dibasic calcium phosphate, dihydrate were added into the V-blenderand mixed about 10 minutes. Magnesium stearate was then added to theblend and mixed for an additional 3 minutes or so. Samples fromdifferent sections of the V-blender were drawn and submitted foranalyzing blend uniformity. A sample from the final blend was analyzedfor particle size distribution, bulk and tap density, flow index, andmoisture studies. The granules were then weighed.

4. Compression of methylcellulose tablets

The final blend was charged into the hopper of a Stokes single punch ‘F’tablet press and compressed into caplets with a suitable tooling. Targethardness desired is between 10 and 25, preferably 8-12 SCU, a preferredtarget weight of each tablet of less than 750 mg; an estimatedfriability of less than 2.0%, more preferably less than 1.0%, and targetdisintegration times below 30 minutes in water and acid (shorterdisintegration times, less than 10 minutes, more preferably less than 8minutes, in 0.1N HCl and less than 15 minutes in water, more preferablyabout 8 minutes, are preferred). The tablets were packaged in Ziplockbags. The tablets were tested for weight variation, hardness,disintegration in acid and water, friability, moisture (% LOD),thickness, viscosity, and content uniformity.

The formulation in TABLE I exhibited a disintegration time of less than5 minutes in 0.1N HCl and less than 9 minutes in water by theconventional USP method using Disintegration Apparatus with disks.

The disintegration time for the formulation of Table 1, Example 1, wasless than 5 minutes in 0.1N HCl was less than 9 minutes in water.

It is noted that Examples 2 to 6, and 11 to 15 are Avicel basedformulations, and Examples 7 to 10 are strach based formulations whichdo not contain an edible calcium salt excipients. These are merely forillustration purposes, and may be formulated to include the ediblecalcium salts as desired using the teachings of this invention andworking examples 1, and 16 to 23.

EXAMPLE 2

A formulation containing both Avicel PH 101® and Explotab®, intra andextragranularly as shown in TABLE II below, exhibited an averagedisintegration time of less than 1 minute in 0.1N HCl at 37^(±)0.5° C.using the automated disintegration apparatus.

TABLE II Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 60.31 Avicel PH 101 ® 0.0370 4.46Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.46 Explotab ®0.0300 3.62 DI water q.s. q.s. Phase B Phase A 0.6055 73.03 Sodiumlauryl sulfate 0.0017 0.21 Sodium starch glycolate 0.0253 3.05 Avicel PH101 ® 0.1880 22.67 Magnesium stearate 0.0086 1.04 TOTAL 0.8291 100.00

EXAMPLE 3

A formulation containing Avicel PH 101® intragranularly, extragranularAvicel PH 102® and Explotab®, intra and extragranularly, as shown belowin TABLE III exhibited an average disintegration time of less than 3minutes in 0.1N HCl at 37^(±)0.5° C. using the automated disintegrationapparatus.

TABLE III Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 59.24 Avicel PH 101 ®0.0370 4.38 Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.03704.38 Explotab ® 0.0300 3.56 Dye/colouring agent 0.0040 0.47 DI waterq.s. q.s. Phase B Phase A 0.6095 72.21 Sodium lauryl sulfate 0.0015 0.18Sodium starch glycolate 0.0220 2.61 Avicel PH 102 ® 0.2035 24.11Magnesium stearate 0.0075 0.89 TOTAL 0.8440 100.00

EXAMPLE 4

A formulation containing Avicel PH 101® intragranularly, extragranularAvicel PH 102® and Explotab® intra and extragranularly as shown in TABLEIV below exhibited an average disintegration time of less than 2 minutesin 0.1N HCl at 37^(±)0.5° C. using the automated disintegrationapparatus.

TABLE IV Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 59.52 Avicel PH 101 ® 0.0370 4.41Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.41 Explotab ®0.0300 3.57 DI water q.s. q.s. Phase B Phase A 0.6055 72.08 Sodiumlauryl sulfate 0.0015 0.18 Sodium starch glycolate 0.0220 2.62 Avicel PH102 ® 0.2035 24.23 Magnesium stearate 0.0075 0.89 TOTAL 0.8400 100.00

In an alternative embodiment of Example 4 a coated version of theformulation shown in TABLE IV was tested for disintegration time. Thecoating solution used was 20% w/w Opadry II, Orange in water. Theaverage disintegration time of coated tablets was less than one minutein 0.1N HCl at 37^(±)0.5° C. using the automated disintegrationapparatus.

EXAMPLE 5

A formulation containing Avicel PH101® intragranularly, extragranularAvicel PH 102® and Explotab® intra and extragranularly as shown in TABLEV exhibited an average disintegration time of less than one minute in0.1N HCl at 37^(±)0.5° C. using the automated disintegration apparatus.

TABLE V Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 60.24 Avicel PH 101 ® 0.0370 4.46Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.46 Explotab ®0.0300 3.62 DI water q.s. q.s. Phase B Phase A 0.6055 72.95 Sodiumlauryl sulfate 0.0015 0.18 Sodium starch glycolate 0.0110 1.33 Avicel PH102 ® 0.2045 24.64 Magnesium stearate 0.0075 0.90 TOTAL 0.8300 100.00

EXAMPLE 6

A formulation containing Avicel PH101® intragranularly, extragranularAvicel PH102® and no Explotab® as shown in TABLE VI below, exhibited anaverage disintegration time of less than 3 minutes in 0.1N HCl and lessthan 2 minutes at 37^(±)0.5° C. using the automated disintegrationapparatus. The disintegration times using the conventional apparatuswere about 1 minute in acid and less than 2 minutes in water.

TABLE VI Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 67.94 Avicel PH 101 ® 0.0370 5.03Sodium lauryl sulfate 0.0015 0.20 Povidone 29K/32 0.0370 5.03Dye/Colouring Agent 0.0010 0.14 DI water q.s. q.s. Phase B Phase A0.5765 78.34 Sodium lauryl sulfate 0.0011 0.15 Avicel PH 102 ® 0.152720.75 Magnesium stearate 0.0056 0.76 TOTAL 0.7359 100.00

EXAMPLE 7

A formulation containing corn starch intragranularly, extragranularStarch 1500 and no Explotab® as shown in TABLE VII exhibited an averagedisintegration time of less than 16 minutes in 0.1N HCl at 37^(±)0.5° C.using the automated disintegration apparatus.

TABLE VII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 63.29  Corn starch 0.03704.68 Sodium lauryl sulfate 0.0015 0.19 Povidone 29K/32 0.0370 4.68Dye/Colouring Agent 0.0010 0.13 DI water q.s. q.s. Phase B Phase A0.5765 72.97  Sodium lauryl sulfate 0.0015 0.19 Starch 1500 ® 0.204525.89  Magnesium stearate 0.0075 0.95 TOTAL 0.7900 100.00 

EXAMPLE 8

A formulation containing corn starch intragranularly, extragranularStarch 1500 and intragranular Explotab® as shown in TABLE VIII exhibitedan average disintegration time of less than 14 minutes in 0.1N HCl at37^(±)0.5° C. using the automated disintegration apparatus.

TABLE VIII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 61.00  Corn starch 0.03704.51 Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.51Explotab ® 0.0300 3.66 Dye/Colouring Agent 0.0010 0.12 DI water q.s.q.s. Phase B Phase A 0.6065 73.98  Sodium lauryl sulfate 0.0015 0.18Starch 1500 ® 0.2045 24.93  Magnesium stearate 0.0075 0.91 TOTAL 0.8200100.00 

EXAMPLE 9

A formulation containing corn starch intragranularly, extragranularStarch 1500 and intra as well as extragranular Explotab® as shown inTABLE IX exhibited an average disintegration time of less than 13minutes in 0.1N HCl at 37^(±)0.5° C. using the automated disintegrationapparatus.

TABLE IX Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 59.88  Corn starch 0.0370 4.43Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.43 Explotab ®0.0300 3.59 Dye/Colouring Agent 0.0010 0.12 DI water q.s. q.s. Phase BPhase A 0.6065 72.63  Sodium lauryl sulfate 0.0015 0.18 Starch 1500 ®0.2045 24.49  Explotab ® 0.0150 1.80 Magnesium stearate 0.0075 0.90TOTAL 0.8350 100.00 

EXAMPLE 10

A formulation containing corn starch intragranulary, extragranularStarch 1500 and intra as well as extragranular Explotab® (in higheramounts than shown above in Example 9, TABLE IX) as shown in TABLE Xexhibited an average disintegration time of less than 11 minutes in 0.1NHCl and less than 18 minutes in water at 37^(±)0.5° C. using theautomated disintegration apparatus.

TABLE X Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 58.82  Corn starch 0.0370 4.35Sodium lauryl sulfate 0.0015 0.18 Povidone 29K/32 0.0370 4.35 Explotab ®0.0300 3.53 Dye/Colouring Agent 0.0010 0.12 DI water q.s. q.s. Phase BPhase A 0.6065 71.35  Sodium lauryl sulfate 0.0015 0.18 Starch 1500 ®0.2045 24.05  Explotab ® 0.0300 3.54 Magnesium stearate 0.0075 0.88TOTAL 0.8500 100.00 

EXAMPLE 11

Various formulation containing Avicel PH 101® intragranularly anddifferent levels of extragranular Avicel PH 102® (as shown in Examples6, 7, and 8 above) were made to observe their effect on disintegrationtime of the tablets.

The formulation in TABLE XI, below, exhibited an average disintegrationtime of less than one minute in 0.1N HCl and less than 2 minutes inwater at 37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 1 minute in bothacid and water.

TABLE XI Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 62.42  Avicel PH 101 ® 0.0370 4.62Sodium lauryl sulfate 0.0015 0.19 Povidone 29K/32 0.0480 5.99Dye/Colouring Agent 0.0010 0.12 DI water q.s. q.s. Phase B Phase A0.5875 73.34  Sodium lauryl sulfate 0.0015 0.19 Avicel PH 102 ® 0.204525.53  Magnesium stearate 0.0075 0.94 TOTAL 0.8010 100.00 

EXAMPLE 12

The formulation in TABLE XII exhibited an average disintegration time ofless than 5 minutes in 0.1N HCl and less than 7 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 5 minutes inacid and less than 8 minutes in water.

TABLE XII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 69.35  Avicel PH 101 ®0.0370 5.13 Sodium lauryl sulfate 0.0015 0.21 Povidone 29K/32 0.04806.66 Dye/Colouring Agent 0.0010 0.14 DI water q.s. q.s. Phase B Phase A0.5875 81.48  Sodium lauryl sulfate 0.0015 0.21 Avicel PH 102 ® 0.124517.27  Magnesium stearate 0.0075 1.04 TOTAL 0.7210 100.00 

EXAMPLE 13

The formulation in TABLE XIII exhibited an average disintegration timeof less than 10 minutes in 0.1N HCl and less than 14 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 14 minutes inacid and less than 22 minutes in water.

TABLE XIII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 76.10  Avicel PH 101 ®0.0370 5.63 Sodium lauryl sulfate 0.0015 0.23 Povidone 29K/32 0.04807.31 Dye/coloring agent 0.0010 0.15 DI water q.s. q.s. Phase B Phase A0.5875 89.42  Sodium lauryl sulfate 0.0015 0.23 Avicel PH 102 ® 0.06059.21 Magnesium stearate 0.0075 1.14 TOTAL 0.6570 100.00 

EXAMPLE 14

Two formulations containing Avicel PH 101® intragranularly withdifferent levels of extragranular Avicel PH 200® (shown in TABLE XIV andXV below) were made to observe the effect on disintegration time oftablets.

The formulation in TABLE XIV exhibited an average disintegration time ofless than 7 minutes in 0.1N HCl and less than 9 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 8 minutes inacid and less than 13 minutes in water.

TABLE XIV Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 62.42  Avicel PH101 ®0.0370 4.62 Sodium lauryl sulfate 0.0015 0.19 Povidone 29K/32 0.04805.99 Dye/Coloring Agent 0.0010 0.12 DI water q.s. q.s. Phase B Phase A0.5875 73.34  Sodium lauryl sulfate 0.0015 0.19 Avicel PH200 ® 0.204525.53  Magnesium stearate 0.0075 0.94 TOTAL 0.8010 100.00 

EXAMPLE 15

The formulation in TABLE XV exhibited an average disintegration time ofless than 4 minutes in 0.1N HCl and less than 7 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 5 minutes inacid and less than 9 minutes in water.

TABLE XV Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 69.35  Avicel PH101 ® 0.0370 5.13Sodium lauryl sulfate 0.0015 0.21 Povidone 29K/32 0.0480 6.66Dye/Coloring Agent 0.0010 0.14 DI water q.s. q.s. Phase B Phase A 0.587581.48  Sodium lauryl sulfate 0.0015 0.21 Avicel PH200 ® 0. 1245 17.27 Magnesium stearate 0.0075 1.04 TOTAL 0.7210 100.00 

EXAMPLE 16

A formulation containing a calcium source from the intragranular andextragranular excipient, dibasic calcium phosphate, dihydrate withextragranular Explotab® is shown in TABLE XVI.

The formulation in TABLE XVI exhibited an average disintegration time ofless than 6 minutes in 0.1N HCl and less than 9 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 5 minutes inacid and less than 12 minutes in water.

TABLE XVI Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 66.93  Dibasic Calciumphosphate, dihydrate 0.0370 4.95 Sodium lauryl sulfate 0.0015 0.20 F, D,and C Yellow #6 0.0010 0.13 Povidone 29K/32 0.0480 6.43 DI water q.s.q.s. Phase B Phase A 0.5875 78.65  Sodium lauryl sulfate 0.0015 0.20Sodium starch glycolate 0.0260 3.48 Dibasic Calcium phosphate, dihydrate0.1245 16.67  Magnesium stearate 0.0075 1.00 TOTAL 0.7470 100.00 

EXAMPLE 17

A formulation containing a calcium source from the intra andextragranular excipient, dibasic calcium phosphate, dihydrate with ahigher amount of extragranular Explotab® than in Example 17, is shownbelow in TABLE XVII.

The formulation in TABLE XVII exhibited an average disintegration timeof less than 9 minutes in 0.1N HCl and less than 14 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus. Theconventional disintegration apparatus yielded less than 6 minutes inacid and less than 12 minutes in water.

TABLE XVII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 65.19  Dibasic Calciumphosphate, dihydrate 0.0370 4.82 Sodium lauryl sulfate 0.0015 0.20 F, D,and C Yellow #6 0.0010 0.13 Povidone 29K/32 0.0480 6.26 DI water q.s.q.s. Phase B Phase A 0.6105 79.60  Sodium lauryl sulfate 0.0015 0.20Sodium starch glycolate 0.0230 3.00 Dibasic Calcium phosphate, dihydrate0.1245 16.23  Magnesium stearate 0.0075 0.97 TOTAL 0.7670 100.00 

EXAMPLE 18

Formulations containing a calcium source from the intra andextragranular excipient, dibasic calcium phosphate, dihydrate withdifferent levels of extragranular Explotab®, in combination with similaramount of intragranular Explotab®, are shown below in TABLE XVIII andXIX (Example 19).

The formulation in TABLE XVIII exhibited an average disintegration timeof less than 6 minutes in 0.1N HCl and less than 11 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus.

TABLE XVIII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 65.19  Dibasic Calciumphosphate, dihydrate 0.0370 4.82 Sodium lauryl sulfate 0.0015 0.20Sodium starch glycolate 0.0230 3.00 F, D, and C Yellow #6 0.0010 0.13Povidone 29K/32 0.0480 6.26 DI water q.s. q.s. Phase B Phase A 0.610579.60  Sodium lauryl sulfate 0.0015 0.20 Sodium starch glycolate 0.02303.00 Dibasic Calcium phosphate, dihydrate 0. 1245 16.23  Magnesiumstearate 0.0075 0.97 TOTAL 0.7670 100.00 

EXAMPLE 19

The formulation in TABLE XIX exhibited an average disintegration time ofless than 9 minutes in 0.1N HCl and less than 14 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus.

TABLE XIX Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 63.86  Dibasic Calciumphosphate, dihydrate 0.0370 4.73 Sodium lauryl sulfate 0.0015 0.19Sodium starch glycolate 0.0230 2.94 F, D, and C Yellow #6 0.0010 0.13Povidone 29K/32 0.0480 6.13 DI water q.s. q.s. Phase B Phase A 0.610577.97  Sodium lauryl sulfate 0.0015 0.19 Sodium starch glycolate 0.03904.98 Dibasic Calcium phosphate, dihydrate 0. 1245 15.90  Magnesiumstearate 0.0075 0.96 TOTAL 0.7830 100.00 

EXAMPLE 20

Formulations containing a calcium source from the intra andextragranular excipient, dibasic calcium phosphate, dihydrate withextragranular Explotab® are shown in TABLE XX and XXI (Example 21)below.

The formulation in TABLE XX exhibited an average disintegration time ofless than 5 minutes in 0.1N HCl and less than 13 minutes in water at37^(±)0.5° C. using the automated disintegration apparatus.

TABLE XX Swallowable Methylcellulose Tablets Formula Ingredient g/tablet(% w/w) Phase A Methocel A4M 0.5000 66.89  Dibasic Calcium phosphate,dihydrate 0.0370 4.95 Sodium lauryl sulfate 0.0015 0.20 F, D, and CYellow #6 0.0010 0.13 Povidone 29K/32 0.0300 4.01 DI water q.s. q.s.Phase B Phase A 0.5695 76.19  Sodium lauryl sulfate 0.0015 0.20 Sodiumstarch glycolate 0.0445 5.95 Dibasic Calcium phosphate, dihydrate 0.124516.66  Magnesium stearate 0.0075 1.00 TOTAL 0.7475 100.00 

EXAMPLE 21

The formulation in TABLE XXI exhibited an average disintegration time ofless than 7 minutes in 0.1N HCl and less than 9 minutes in water at37^(±)0.5° C. using the conventional disintegration method.

TABLE XXI Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 64.52  Dibasic Calciumphosphate, dihydrate 0.0370 4.77 Sodium lauryl sulfate 0.0015 0.19 F, D,and C Yellow #6 0.0010 0.13 Povidone 29K/32 0.0480 6.19 DI water q.s.q.s. Phase B Phase A 0.5875 75.81  Sodium lauryl sulfate 0.0015 0.19Sodium starch glycolate 0.0235 3.03 Dibasic Calcium phosphate, dihydrate0.1550 20.00  Magnesium stearate 0.0075 0.97 TOTAL 0.7750 100.00 

EXAMPLE 22

A formulation containing a calcium source from the intra andextragranular excipient, calcium phosphate, anhydrous with extragranularExplotab® is indicated in TABLE XXII.

The formulation in TABLE XXII exhibited an average disintegration timeof less than 11 minutes in 0.1N HCl and less than 19 minutes in water at37^(±)0.5° C. using the conventional disintegration apparatus.

TABLE XXII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 66.93  Calcium phosphate,Anhydrous 0.0370 4.95 Sodium lauryl sulfate 0.0015 0.20 F, D, and CYellow #6 0.0010 0.13 Povidone 29K/32 0.0480 6.43 DI water q.s. q.s.Phase B Phase A 0.5875 78.65  Sodium lauryl sulfate 0.0015 0.20 Sodiumstarch glycolate 0.0260 3.48 Calcium phosphate, Anhydrous 0. 1245 0.67Magnesium stearate 0.0075 1.00 TOTAL 0.7470 100.00 

EXAMPLE 23

A formulation containing a calcium source from the intra andextragranular excipient, tribasic calcium phosphate WG® withextragranular Explotab® is indicated in TABLE XXIII.

The formulation in TABLE XXIII exhibited an average disintegration timeof less than 13 minutes in 0.1N HCl and less than 24 minutes in water at37^(±)0.5° C. using the conventional disintegration apparatus.

TABLE XXIII Swallowable Methylcellulose Tablets Formula Ingredientg/tablet (% w/w) Phase A Methocel A4M 0.5000 66.93  Tribasic Calciumphosphate, WG ® 0.0370 4.95 Sodium lauryl sulfate 0.0015 0.20 F, D, andC Yellow #6 0.0010 0.13 Povidone 29K/32 0.0480 6.43 DI water q.s. q.s.Phase B Phase A 0.5875 78.65  Sodium lauryl sulfate 0.0015 0.20 Sodiumstarch glycolate 0.0260 3.48 Tribasic Calcium phosphate, WG ® 0.124516.67  Magnesium stearate 0.0075 1.00 TOTAL 0.7470 100.00 

All publications, including but not limited to patents and patentapplications, cited in this specification are herein incorporated byreference as if each individual publication were specifically andindividually indicated to be incorporated by reference herein as thoughfully set forth.

The above description fully discloses the invention including preferredembodiments thereof. Modifications and improvements of the embodimentsspecifically disclosed herein are within the scope of the followingclaims. Without further elaboration, it is believed that one skilled inthe art can, using the preceding description, utilize the presentinvention to its fullest extent. Therefore the Examples herein are to beconstrued as merely illustrative and not a limitation of the scope ofthe present invention in any way. The embodiments of the invention inwhich an exclusive property or privilege is claimed are defined asfollows.

What is claimed is:
 1. A rapidly disintegrating tablet for oraladministration which tablet comprises a compacted mixture ofmethylcellulose having a viscosity of >1000 centipoise; and an ediblecalcium salt selected from the group consisting of dibasic calciumphosphate dihydrate, calcium phosphate anhydrous, and tribasic calciumphosphate; or mixtures thereof.
 2. A rapidly disintegrating tablet fororal administration which tablet comprises methylcellulose having aviscosity of >3000 centipoise; dibasic calcium phosphate, sodium laurylsulfate, povidone; sodium starch glycolate, and magnesium stearate. 3.The tablet according to claim 1 which further comprises a binding agent.4. The tablet according to claim 3 wherein the binding agent is selectedfrom the group consisting of PVP, hydroxypropylcellulose, hydroxypropylmethylcellulose, acacia, gelatin, tragacanth, pregelatinized starch andstarch.
 5. The tablet according to claim 4 wherein the binding agent isPVP.
 6. The tablet according to claim 1 which further comprises adisintegrating agent.
 7. The tablet according to claim 6 wherein thedisintegrating agent is selected from the group consisting of sodiumstarch glycolate, sodium carboxymethylcellulose, sodium crosscarmellose,carboxymethylcellulose, veegum, an alginate, agar, guar, tragacanth,locust bean, karaya, pectin, and crospovidone.
 8. The tablet accordingto claim 7 wherein the disintegrating agent is sodium starch glycolate.9. The tablet according to claim 8 wherein the sodium starch glycolateis present in an amount of about 3 to about 8% w/w.
 10. The tabletaccording to claim 1 which further comprises a wetting agent.
 11. Thetablet according to claim 10 wherein the wetting agent is sodium laurylsulfate.
 12. The tablet according to claim 1 which further comprises alubricating agent.
 13. The tablet according to claim 12 wherein thelubricating agent is magnesium stearate.
 14. The tablet according toclaim 1 wherein the methylcellulose has a viscosity of >2000centipoises.
 15. The tablet according to claim 14 wherein themethylcellulose has a viscosity of >3000 centipoises.
 16. The tabletaccording to claim 15 wherein the methylcellulose has a viscosityof >4000 centipoises.
 17. A process for preparing a tablet formulationwhich comprises compacting a mixture of a) blending together to form anintragranular mixture high viscosity methylcellulose of >3000 cps, awetting agent, povidone or sodium starch glycolate, and an ediblecalcium salt; and b) adding to the mixture of step (a) a PVP aqueoussolution, or alternatively spraying the mixture of step (a) with a PVPaqueous solution; and preparing granulates; and c) blending together anextragranular mixture of an edible calcium salt, a wetting agent; alubricating agent; povidone or sodium starch glycolate or a mixturethereof; and d) compacting the granulates of step (b) with theextragranular mixture of step (c).
 18. The tablet according to claim 1wherein the edible calcium salt is Dibasic calcium phosphate dihydrateand is present in a ratio of methylcellulose to calcium from about 2 toabout 4:1.
 19. The tablet according to claim 1 wherein the ediblecalcium salt is Calcium phosphate, anhydrous and is present in a ratioof methylcellulose to calcium from about 2 to about 4:1.
 20. The tabletaccording to claim 1 wherein the edible calcium salt is Tribasic calciumphosphate and is present in a ratio of methylcellulose to Tribasiccalcium phosphate, from about 2 to about 4:1.
 21. The tablet accordingto claim 1 which further comprises additional excipents and diluents inthe ratio of: Sodium lauryl sulfate:Explotab:Tribasic calciumphosphate:Povidone 29K/32:Magnesium stearate include:0.40:3.5:21.6:6.4:1.0; or Sodium lauryl sulfate:Explotab:Calciumphosphate, anhydrous:Povidone 29K/32:Magnesium stearate include:0.40:3.5:21.6:6.4:1.0.
 22. The tablet according to claim 1 wherein themethylcellulose is present in an amount of about 450 to about 550 mg.23. The tablet according to claim 1 wherein the methylcellulose ispresent in an amount of about 200 to about 300 mg.
 24. A process for themanufacture of a pharmaceutical tablet, which process comprises mixinga) granulates comprising high viscosity methylcellulose of >3000 cps, awetting agent, povidone or sodium starch glycolate, an edible calciumsalt; and b) blending together an extragranular mixture of an ediblecalcium salt, a wetting agent; a lubricating agent; povidone or sodiumstarch glycolate or a mixture thereof; and c) compacting the granulatesof step (b) with the granular mixture of step (a); and d) compressinginto a tablet.
 25. A rapidly disintegrating tablet for oraladministration which tablet comprises a compacted mixture ofmethylcellulose having a viscosity of >1000 centipoise; and an ediblecalcium salt wherein the ratio of methylcellulose to calcium salt isfrom about 2:1 to about 4:1.
 26. The process according to claim 17wherein the edible calcium salt is selected from the group consisting ofdibasic calcium phosphate dihydrate, calcium phosphate anhydrous, andtribasic calcium phosphate; or mixtures thereof.
 27. The processaccording to claim 26 wherein the edible calcium salt is dibasic calciumphosphate dihydrate.
 28. The tablet according to claim 25 which furthercomprises a wetting agent.
 29. The tablet according to claim 5 whereinthe PVP is present in an amount of about 4 to about 6.5% w/w.
 30. Aprocess for the preparation of granulates which comprises a) blendingtogether a high viscosity methylcellulose of >3000 cps, a wetting agent,and an edible calcium salt; and b) adding to the mixture of step (a) apolyvinylpyrrolidone aqueous solution, or alternatively spraying themixture of step (a) with a polyvinylpyrrolidone aqueous solution; andpreparing a granulate.
 31. The process according to claim 30 wherein theedible calcium salt is dibasic calcium phosphate dihydrate, calciumphosphate anhydrous, tribasic calcium phosphate; or mixtures thereof.32. The process according to claim 31 wherein the granulate is admixedwith a second wetting agent, a lubricating agent, and a disintegrant,and compressed to form a tablet.
 33. The process according to claim 32wherein the disintegrant is selected from the group consisting of sodiumstarch glycolate, sodium carboxymethylcellulose, sodium crosscarmellose,carboxymethylcellulose, veegum, alginates, agar, guar, tragacanth,locust bean, karaya, pectin, and crospovidone.
 34. The process accordingto claim 30 wherein the wetting agent is sodium lauryl sulfate.
 35. Theprocess according to claim 32 wherein the second wetting agent is sodiumlauryl sulfate.
 36. The process according to claim 30 wherein thegranulate further comprises a diluent.
 37. The process according toclaim 36 wherein the diluent is microcrystalline cellulose, Corn Starchor Starch
 1500. 38. The process according to claim 30 wherein thegranulate further comprises a disintegrant.
 39. The process according toclaim 36 wherein the disintegrant is sodium starch glycolate.
 40. Theprocess according to claim 33 wherein the second disintegrant is sodiumstarch glycolate.
 41. The process according to claim 36 wherein thelubricating agent is magnesium stearate.
 42. The tablet according toclaim 28 wherein the wetting agent is sodium lauryl sulfate.
 43. Thetablet according to claim 25 wherein the ratio of methylcellulose tocalcium salt is from about 2:6 to 3.1:1.
 44. The tablet according toclaim 25 wherein the edible calcium salt is dibasic calcium phosphatedihydrate, calcium phosphate anhydrous, tribasic calcium phosphate; ormixtures thereof.
 45. The tablet according to claim 43 which furthercomprises a binding agent.
 46. The tablet according to claim 45 whereinthe binding agent is selected from the group consisting of PVP,hydroxypropylcellulose, hydroxypropyl methylcellulose, acacia, gelatin,tragacanth, pregelatinized starch and starch.
 47. The tablet accordingto claim 46 wherein the binding agent is PVP.
 48. The tablet accordingto claim 25 which further comprises a disintegrating agent.
 49. Thetablet according to claim 48 wherein the disintegrating agent isselected from the group consisting of sodium starch glycolate, sodiumcarboxymethylcellulose, sodium crosscarmellose, carboxymethylcellulose,veegum, an alginate, agar, guar, tragacanth, locust bean, karaya,pectin, and crospovidone.
 50. The tablet according to claim 49 whereinthe disintegrating agent is sodium starch glycolate.
 51. The tabletaccording to claim 50 wherein the sodium starch glycolate is present inan amount of about 3 to about 8% w/w.
 52. The tablet according to claim25 which further comprises a lubricating agent.
 53. The tablet accordingto claim 52 wherein the lubricating agent is magnesium stearate.
 54. Thetablet according to claim 25 wherein the methylcellulose has a viscosityof >2000 centipoises.
 55. The tablet according to claim 54 wherein themethylcellulose has a viscosity of >3000 centipoises.
 56. The tabletaccording to claim 55 wherein the methylcellulose has a viscosityof >4000 centipoises.
 57. The tablet according to claim 47 wherein thePVP is present in an amount of about 4 to about 6.5% w/w.